Keratinocyte growth factor (KGF) is a stromally secreted growth factor that stimulates proliferation only in epithelial cells. Previously we showed that KGF mRNA and protein were greatly increased in the macaque endometrium after progesterone (P) treatment suggesting that KGF may function as a progestomedin. We have further shown by RT-PCR that KGF receptor (KGFR) mRNA is also present in the endometrium. In this study we used a unique chimeric KGF-HFC molecule containing KGF and the hinge region-FC portion of an IgG molecule as a probe to detect the KGFR protein immunohistochemically. Uteri were collected from spayed monkeys that were treated with estradiol (E2) alone for 14 days, or E2 plus P (14 days E2, then 14 days E2 plus P). Fresh tissues were immediately frozen in liquid propane and stored in liquid nitrogen. Cryostat sections of endometrium were incubated with the chimeric KGF-HFC molecule. KGF-HFC, bound to the KGFR through its KGF link, was then reacted with an anti-IgG biotinylated second antibody, and detected with an avidin-biotin kit. KGFR was localized to the epithelial cells of endometrial glands, and to smooth muscle elements of the endometrial arteries. After E2 treatment, KGFR staining was distributed along the basal surface of glandular epithelial cells of the upper and mid functionalis. However, after exposure to P, staining was more localized to basal surface of glands of the endometrial basalis. These results support our hypothesis that KGF acts as a stromal mediator of epithelial proliferation in the endometrial basalis under P. KGFR localization on smooth muscle cells of the spiral arteries suggests that KGF may also be involved in stimulating spiral artery growth. Further investigation on KGF stimulation of spiral artery development is warranted.